Sample analyzer

ABSTRACT

A sample analyzer comprising: a sample preparing section for preparing first and second measurement sample including reagent and sample; a first detector for detecting a predetermined component in the first measurement sample prepared by the sample preparing section; a second detector for detecting the predetermined component in the second measurement sample prepared by the sample preparing section; and a controller configured for performing operations, comprising: (a) controlling the first detector to detect the predetermined component in the first measurement sample prepared by the sample preparing section; (b) determining the reliability of the result detected by the first detector; (c) controlling the sample preparing section to prepare the second measurement sample from the same sample when the result has been determined to be unreliable; and (d) controlling the second detector to detect the predetermined component in the second measurement sample, is disclosed.

FIELD OF THE INVENTION

The present invention relates to a sample analyzer for analyzingpredetermined components in a sample such as blood, urine and the like.

BACKGROUND

Many sample analyzers have been developed for measuring the size ofpredetermined component particles in a sample such as blood, urine andthe like, and analyzing the state of the particle distributions.Particularly in sample analyzers for detecting the distribution statesof red blood cells, white blood cells, platelets and the like, red bloodcells and platelets are measured by using an electrical resistance typemeasuring device since platelets have a relatively small size of 1 to 4μm compared to the size of red blood cells which are 7 to 8 μm.

However, small size red blood cells may exits. Also, collapsed red bloodcells have smaller size than usual. In those cases, red blood cells andplatelets can not be reliably differentiated simply by the size.

Japanese Laid-Open Patent Publication No. 2000-275163 discloses aparticle analyzer which produces highly reliable measurement results bymeasuring platelets by using both an electrical resistance typemeasuring device and an optical measuring device. This particle analyzeradopts more reliable platelet number between a platelet number by theelectrical resistance type measuring device and a platelet number by theoptical measuring device.

In the particle analyzer disclosed in Japanese Laid-Open PatentPublication No. 2000-275163, however, two types of measurement samplesallocated from the same sample must be prepared, and the measurementsare performed by the electrical resistance type measuring device and theoptical type measuring device using the respective measurement samples.Disadvantages thus arise relating to the cost of the reagents used inthe preparations, and the simple doubling of the number of measurementprocesses, which make it difficult to reduce analysis costs.

SUMMARY OF THE INVENTION

The scope of the present invention is defined solely by the appendedclaims, and is not affected to any degree by the statements within thissummary.

A first aspect of the present invention is a sample analyzer comprising:a sample preparing section for preparing first and second measurementsample including reagent and sample; a first detector for detecting apredetermined component in the first measurement sample prepared by thesample preparing section; a second detector for detecting thepredetermined component in the second measurement sample prepared by thesample preparing section; and a controller configured for performingoperations, comprising: (a) controlling the first detector to detect thepredetermined component in the first measurement sample prepared by thesample preparing section; (b) determining the reliability of the resultdetected by the first detector; (c) controlling the sample preparingsection to prepare the second measurement sample from the same samplewhen the result has been determined to be unreliable; and (d)controlling the second detector to detect the predetermined component inthe second measurement sample.

A second aspect of the present invention is a sample analyzercomprising: a sample preparing section for preparing first and secondmeasurement sample including reagent and sample; a first detector fordetecting a predetermined component in the first and second measurementsample prepared by the sample preparing section; and a controllerconfigured for performing operations, comprising: (a) controlling thefirst detector to detect the predetermined component in the firstmeasurement sample prepared by the sample preparing section using afirst detection condition; (b) determining the reliability of the resultdetected by the first detector; (c) controlling the sample preparingsection to prepare the second measurement sample from the same samplewhen the result has been determined to be unreliable; and (d)controlling the first detector to detect the predetermined component inthe second measurement sample using a second detection condition whichis different from the first detection condition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram showing the structure of a first embodiment ofthe sample analyzer of the present invention;

FIG. 2 is a perspective view showing the internal structure of the bodyof the first embodiment of the sample analyzer of the present invention;

FIG. 3 is an elevation view showing the internal structure of the bodyof the first embodiment of the sample analyzer of the present invention;

FIG. 4 is a fluid channel diagram of the sample analyzer of the firstembodiment;

FIG. 5 is a fluid channel diagram of the sample analyzer of the firstembodiment;

FIG. 6 is a fluid channel diagram of the sample analyzer of the firstembodiment;

FIG. 7 is a fluid channel diagram of the sample analyzer of the firstembodiment;

FIG. 8 is a block diagram showing the structure of a first embodiment ofthe operation and display device of the present invention;

FIG. 9 is a modal view showing the main structure of a first measuringdevice, which is an electrical resistance type measuring device;

FIG. 10 is a modal view showing the main structure of a third measuringdevice, which is an optical type measuring device;

FIG. 11 is a flow chart showing the sequence of CPU processing of theoperation and display device of the first embodiment of the sampleanalyzer of the present invention;

FIG. 12 shows an illustration of the reliability determination based ona histogram;

FIG. 13 shows an illustration of a histogram based on PLT measurementdata;

FIG. 14 is a flow chart showing the sequence of the reliabilitydetermination process of the operation and display device of the firstembodiment of the sample analyzer of the present invention;

FIG. 15 shows an illustration of a scattergram representing the PLTre-measurement results of the first embodiment of the sample analyzer ofthe present invention;

FIG. 16 is a flow chart showing the sequence of CPU processing of theoperation and display device of a second embodiment of the sampleanalyzer of the present invention;

FIG. 17 is a flow chart showing the sequence of the reliabilitydetermination process of the operation and display device of the secondembodiment of the sample analyzer of the present invention;

FIG. 18 shows an illustration of a scattergram representing the resultsof a single PLT measurement by the third measuring device of the secondembodiment of the sample analyzer of the present invention;

FIG. 19 shows an illustration of a scattergram representing the resultsof a single PLT measurement by the third measuring device of the secondembodiment of the sample analyzer of the present invention; and

FIG. 20 shows an illustration of a scattergram representing the resultsof a second PLT measurement by the third measuring device of the secondembodiment of the sample analyzer of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The embodiments are described in detail below by way of example of ablood analyzer for analyzing blood used as a sample analyzer withreference to the drawings.

First Embodiment

FIG. 1 is a block diagram showing the structure of a first embodiment ofthe sample analyzer of the present invention. The sample analyzer of thefirst embodiment of the present invention is configured by connecting ananalyzer body 1 and an operation and display device 2 so as to becapable of data communication. The operation and display device 2 hassample analysis software installed for various types of setting relatedto analysis, displaying analysis results and the like; instructions aretransmitted to the analyzer body 1 and measurement data are receivedfrom the analyzer body 1 via data communication between the analyzerbody 1 and the operation and display device 2.

FIG. 2 is a perspective view showing the internal structure of theanalyzer body 1 of the first embodiment of the present invention, andFIG. 3 is a frontal view showing the internal structure of the analyzerbody 1 of the first embodiment of the present invention. The analyzerbody 1 is a blood analyzer for analyzing (measuring analyzing and thelike) blood (sample) contained in a sealed container (initial containerof a measurement sample) collection tube 3, and is provided with asample placement section for placing the collection tube 3 at apredetermined position within the analyzer body 1, a sample preparingsection for preparing a measurement sample by measuring and diluting theblood within the collection tube 3, and measuring units D1, D2, D3 formeasuring the diluted blood.

The sample preparing section is provided with an aspirating tube(aspirator) 14 for piercing a cap 3 a sealing the interior of thecollection tube 3 and aspirating the sample within the collection tube3, which is disposed at a position for preparing a sample for variousanalyses by aspirating a predetermined amount of blood from within thecollection tube 3 and mixing reagent within a first mixing chamber(first container: HGB/RBC chamber) MC1, second mixing chamber (secondcontainer: WBC chamber) MC2, third mixing chamber (third container: RETchamber) MC3, or fourth mixing chamber (fourth container: PLT chamber)MC4, a horizontal drive section for horizontally moving the aspiratingtube 14, and a vertical drive section for vertically moving theaspirating tube 14. Note that the horizontal drive section is providedwith a stepping motor (horizontal drive motor) 69 as a drive source, andthe vertical drive section is provided with a stepping motor (verticaldrive motor) 68 as a drive source. Although the aspirating tube 14 has aflow channel extending through its interior in the longitudinaldirection, and has an aspiration orifice formed near the tip foraspirating a sample or air, the present invention is not particularlylimited to this arrangement.

FIGS. 4 and 5 are fluid channel diagrams of the analyzer body 1 of thefirst embodiment. As shown in FIGS. 4 and 5, reagent containersaccommodating a reagent are provided in the analyzer body 1 and thereagent container is connected to the fluid channel. Specifically, thereagent containers used in the first embodiment are a dilution liquidcontainer EPK-V for accommodating dilution liquid (cleaning liquid) EPK,hemoglobin hemolytic agent container SLS-V for accommodating hemoglobinhemolytic agent SLS, white blood cell classifying hemolytic agentcontainer (common reagent container) FFD-V for accommodating white bloodcell classifying hemolytic agent FFD for dissolving red blood cells, andwhite blood cell classifying stain container (special reagent container)FFS-V for accommodating white blood cell classifying stain FFS.

FIG. 6 is a fluid channel diagram provided with the RET measurementchamber MC3 of the analyzer body 1 of the first embodiment. Similar toFIGS. 4 and 5, reagent containers accommodating a reagent can beprovided in the analyzer body 1 and the reagent containers may beconnected to the fluid channel. The fluid channel provided with the RETmeasurement chamber MC3 is provided with a reticulocyte stain containerRES-V for containing stain RES used to stain reticulocytes, andreticulocyte diluting liquid container RED-V for containing dilutingliquid RED used for reticulocyte measurement.

FIG. 7 is a fluid channel diagram provided with the PLT measurementchamber MC4 of the analyzer body 1 of the first embodiment. Similar toFIGS. 4 and 5, reagent containers accommodating a reagent can beprovided in the analyzer body 1 and the reagent containers may beconnected to the fluid channel. The fluid channel provided with the PLTmeasurement chamber MC4 is provided with a platelet stain containerPLS-V for containing stain PLS used to stain platelets, and plateletdiluting liquid container PLD-V for containing diluting liquid PLD usedfor platelet measurement. The platelet stain container PLS-V contains,for example Nile Blue as a stain.

The aspirating tube 14, whole blood aspirating syringe pump SP1, andsample supplying syringe pump SP2 are provided as a sample supplier forsupplying a sample from the collection tube 3 to the first mixingchamber MC1 and/or second mixing chamber MC2. The aspirating tube 14moves to the first mixing chamber MC1 and second mixing chamber MC2 whena predetermined amount of whole blood has been aspirated from thecollection tube 3 by the whole blood aspirating syringe pump SP1 andsample supplying syringe pump SP2. Then, the predetermined amount ofwhole blood sample is distributed to the first mixing chamber MC1 andsecond mixing chamber MC2, respectively, by the whole blood aspiratingsyringe pump SP1 and sample supplying syringe pump SP2. Note that duringRET measurement, the whole blood sample is also supplied to the thirdmixing chamber MC3.

Part of the whole blood sample is supplied to the fourth mixing chamberMC4 and temporarily stored. When the reliability of the samplemeasurement data has been determined to be low via a method which isdescribed later, instructions are first issued to again prepare a sampleand the diluting liquid PLD and stain PLS are supplied to the fourthmixing chamber MC4.

The dilution liquid container EPK-V and the hemoglobin hemolytic agentcontainer SLS-V are connected so as to be capable of supplying reagentto the first mixing chamber MC1. That is, an EPK diaphragm pump DP1configures the diluting liquid reagent supplying section whereby thediluting liquid can be supplied from the diluting liquid container EPK-Vto the first mixing chamber MC1 by the diluting liquid supplying (EPK)diaphragm pump DP1. An SLS diaphragm pump DP3 configures the hemolyticreagent supplying section whereby the hemoglobin hemolytic agent can besupplied from the hemoglobin hemolytic agent container SLS-V to thefirst mixing chamber MC1 by the hemolytic agent supplying (SLS)diaphragm pump DP3.

The hemolytic agent container FFD-V and stain container FFS-V areconnected so as to supply reagent to the second mixing chamber MC2. Thatis, the hemolytic agent can be supplied from the hemolytic agentcontainer FFD-V to the second mixing chamber MC2 via a hemolytic agentsupplying (FFD) diaphragm pump DP4; the hemolytic agent supplying (FFD)diaphragm pump DP4 configures a hemolytic agent reagent supplyingsection. The stain can be supplied from the stain container FFS-V to thesecond mixing chamber MC2 via the stain (FFS) diaphragm pump DP5; theFFS stain diaphragm pump DP5 configures a stain reagent supplyingsection (special reagent supplying section).

As shown in FIGS. 4 and 5, the reagent supplying channel from thedilution liquid container EPK-V to the first mixing chamber MC1 and thereagent supplying channel from the hemolytic agent container SLS-V tothe first mixing chamber MC1 are joined at a midway confluence pointCR1, forming a common reagent supplying channel T1 for both reagentswhich is connected to the first mixing chamber MC1. Although two typesof reagent are supplied to the first mixing chamber MC1, there may beonly a single reagent supplying orifice to the first mixing chamber MC1,thus simplifying the structure.

As shown in FIG. 5, the reagent supplying channel from the hemolyticagent container FFD-V to the second mixing chamber MC2 and the reagentsupplying channel from the stain container FFS-V to the second mixingchamber MC2 are joined at a midway confluence point CR2, forming acommon reagent supplying channel T2 for both reagents which is connectedto the second mixing chamber MC2. Although two types of reagent aresupplied to the second mixing chamber MC2, there may be only a singlereagent supplying orifice to the second mixing chamber MC2, thussimplifying the structure. Note that the reagent supplying channels T1and T2 may also be provided for each reagent. That is, two reagentsupplying orifices may also be provided for each chamber MC1 and MC2.

The first measuring unit (detector, first detector) D1 performsmeasurements relating to red blood cells and platelets, and the secondmeasuring unit D2 performs measurements relating to hemoglobin. Thethird measuring unit (other detector, second detector) D3 performsmeasurements relating to white blood cells. The first mixing chamber MC1is a part for preparing a sample for analyses relating to red bloodcells, platelets, and hemoglobin; the measurement sample prepared by thefirst mixing chamber MC1 is used in measurements performed by the firstmeasuring unit D1 and second measuring unit D2. The second mixingchamber MC2 is a part for preparing a sample for analyses relating towhite blood cells; the measurement sample prepared by the second mixingchamber MC2 is used in measurements performed by the third measuringunit D3.

The first measuring unit D1 is configured as an RBC/PLT detector forperforming RBC measurements (measuring red blood cell count), and PLTmeasurements (measuring platelet count). The first measuring unit D1 canperform RBC and PLT measurements via a sheath flow DC detection method,and is a so-called electrical resistance measuring device.

The second measuring unit D2 is configured as an HGB detector forperforming HGB measurements (measuring the amount of pigment in theblood). The second measuring unit D2 can perform HGB measurements via anSLS-hemoglobin method.

The third measuring unit D3 is configured as an optical detector capableof performing WBC measurements (white blood cell count), RETmeasurements (reticulocyte count), and PLT measurements (plateletcount). The third measuring unit D3 performs WBC measurements, RETmeasurements, and PLT measurements by flow cytometry using asemiconductor laser, and is a so-called optical type measuring device.

The analyzer body 1 is provided with a controller 11 for controlling theoperations of the sample preparing section, first measuring unit D1,second measuring unit D2, and third measuring unit D3. The analyzer body1 is also provided with a drive circuit 12 for driving theelectromagnetic valves SV1 through SV33, SV40, and SV41 disposed in thefluid channels configuring the sample preparing section, various typesof pump motors 68, 69, SP1, SP2, P, V, DP1 through DP5 and the like; thecontroller 11 drives the electromagnetic valves and the like via thedrive circuit 12. The controller (detector controller) 11 is capable ofdata communication with the operation and display device 2, so as tosend and receive various types of signals and data to/from the operationand display device 2 through a communication interface 13.

FIG. 8 is a block diagram showing the structure of a first embodiment ofthe operation and display device of the present invention. As shown inFIG. 8, the operation and display device 2 is configured by a CPU(central processing unit) 21, RAM 22, memory device 23, input device 24,display device 25, output device 26, communication interface 27,portable disk drive 28, and an internal bus 29 connecting all theabove-mentioned hardware. The CPU 21 is connected to the varioushardware of the operation and display device 2 mentioned above via theinternal bus 29, and controls these various hardware components andperforms various software functions according to a computer program 90stored on the memory device 23. The RAM 22 is configured by a volatilememory such as an SRAM, SDRAM or the like, and is used for developingmodules during the execution of the computer program 90, and fortemporarily storing data generated during the execution of the computerprogram 90.

The memory device 23 may be configured by a built-in fixed type memorydevice (hard disk), volatile memory such as an SRAM, or nonvolatilememory such as a ROM. The computer program 90 stored on the memorydevice 23 may be downloaded from a portable memory medium 80 such as aDVD, CD-ROM or the like which stores information such as programs anddata via the portable disk drive 28, and developed from the memorydevice 23 to the RAM 22 during execution. Of course, the computerprogram 90 may also be downloaded from an external computer connectedvia the communication interface 27.

The memory device 23 is provided with a measurement result storage part231 for storing the measurement results of the first measuring unit D1,second measuring unit D2, and third measuring unit D3; the CPU 21determines the reliability of the detection results based on the storedmeasurement results.

The communication interface is connected to the internal bus 29, and iscapable of sending and receiving data via a communication line connectedto the analyzer body 1. That is, instruction information to start ameasurement can be sent to the analyzer body 1 and measurement data suchas measurement results and the like can be received.

The input device 24 is a data input medium such as a keyboard and mouseor the like. The display device 25 is a CRT monitor, LCD or similardisplay device for graphically displaying analysis results. The outputdevice 26 is a printing device such as a laser printer, inkjet printeror the like.

The analyzer body 1 has two measurement modes relating to themeasurement of platelets in the blood of a measurement sample. The firstmeasurement mode is the CBC measurement mode in which RBC measurementsand PLT measurements are performed by the first measuring unit D1, andWBC measurements art performed by the third measuring unit D3. Thesecond measurement mode is the CBC+RET measurement mode in which RBCmeasurements and PLT measurements are performed by the first measuringunit D1, and the WBC measurements, RET measurements, and PLTmeasurements are performed by the third measuring unit D3. That is, thePLT measurements are performed by both the electrical resistance typemeasuring device and the optical type measuring device.

The operation of the sample analyzer is described below when the CBCmeasurement mode (first measurement mode) has been selected in the firstembodiment. In the analyzer body 1 of the first embodiment, when the CBCmeasurement mode has been selected, the RBC measurement and PLTmeasurement is performed by the first measuring device (detector, firstdetector) D1 which is an electrical resistance type measuring device,and the WBC measurements are performed by the third measuring unit(other detector, second detector) D3 which is an optical type measuringdevice.

FIG. 9 is a modal view showing the main structure of a first measuringunit D1, which is an electrical resistance type measuring device. Thefirst measuring unit D1 has a reactor 111; the blood sample aspirated bythe aspirating tube 14, and introduced together with diluting liquidinto the reactor 111.

A flow channel 112 extends from the reactor 111, and a sheath flow cell113 is provided at the end of the flow channel 112. The measurementsample diluted in the reactor 111 is delivered to the sheath flow cell113 through the flow channel 112. The first measuring unit D1 isprovided with a sheath liquid chamber that is not shown in the drawing,so that the sheath fluid stored in the sheath fluid chamber can besupplied to the sheath flow cell 113.

In the sheath flow cell 113, a flow is formed in which the measurementsample is encapsulated by the sheath fluid. The sheath flow cell 113 isprovided with an orifice 114, the flow of the measurement sample isconstricted by the orifice 114 so that the particles (tangible material)contained in the measurement sample pass one by one through the orifice114. The sheath flow cell 113 is provided with a pair of electrodes 115which are disposed so as to have the orifice 114 interposedtherebetween. A direct current (DC) power source 116 is connected to thepair of electrodes 115 to supply a DC current between the pair ofelectrodes 115. Then, the impedance is detected between the pair ofelectrodes 115 while the DC current is supplied from the DC power source116.

The electrical resistance signals representing the change in impedanceare amplified by an amp 117 and transmitted to the controller 11. Themagnitude of the electrical resistance signal corresponds to the volume(size) of the particle; thus the volume of the particle can be obtainedwhen the controller 11 performs signal processing of the electricalresistance signal.

FIG. 10 is a modal view showing the structure of the third measuringunit D3, which is an optical type measuring device. The third measuringunit D3 receives the measurement sample at a flow cell 301, a flow isformed in the flow cell 301, the blood cells contained in the flowpassing within the flow cell 301 are irradiated by a semiconductor laserlight, and the blood cells are measured. The third measuring unit D3 hasa sheath flow system 300, beam spot system 310, forward scattered lightreceiving system 320, side scattered light receiving system 330, andside fluorescent light receiving system 340.

The sheath flow system 300 forms a flow in which the blood cellscontained in the measurement sample are aligned in a single row withinthe flow cell 301, thus improving the accuracy and reproducibility ofthe blood cell count. The beam spot system 310 is configured so thatlight emitted from the semiconductor laser 311 passes through acollimator lens 312 and condenser lens 313, and irradiates the flow cell301. The beam spot system 310 is also provided with a beam stopper 314.

The forward scattered light receiving system 320 is configured so thatthe forward scattered light is collected by a forward collector lens321, and the light passing through a pinhole 322 is received by aforward scattered light receiver (photodiode) 323, and the signal outputfrom the forward scattered light receiver 323 according to the amount ofreceived light is amplified by an amplifier 324. The amplificationfactor of the amplifier 324 is set by the CPU 21.

The side scattered light receiving system 330 is configured so that theside scattered light is collected by a side scattered light collectorlens 331, and part of the light is reflected by a dichroic mirror 332,received by a side scattered light receiver (photodiode) 333, and thesignal output from the side scattered light receiver 333 according tothe amount of received light is amplified by an amplifier 334. Theamplification factor of the amplifier 334 is set by the CPU 21.

The scattered light is a phenomenon which occurs due to the change inthe direction of travel of the light caused by the presence of anobstacle in the direction in which the light is traveling, that is, aparticle, such as a blood cell. Information relating to the size andmaterial quality of the particle can be obtained by detecting thescattered light. Particularly information relating to the size of theparticle (blood cell) can be obtained from the forward scattered light.Information relating to the interior of the particle, such asinformation concerning the material quality of the particle, can beobtained from the side scattered light.

The side fluorescent light receiving system 340 is configured so thatthe light passing through the dichroic mirror 332 then passes through aspectral filter 341 and is received by a fluorescent light receiver(photomultiplier) 342, and the signal output from the fluorescent lightreceiver 342 according to the amount of received light is amplified byan amplifier 344. The amplification factor of the amplifier 344 is setby the CPU 21.

When a fluorescent material such as a stained blood cell is irradiatedwith light, the fluorescent material generates light that has a longerwavelength than the irradiating light. The fluorescent intensity becomesstronger under heavy staining, so that information relating to thedegree of staining of the blood cell can be obtained by measuring theintensity of the fluorescent light. Other measurements such as theclassification of the blood cell can be performed via the differences inthe side fluorescent light intensity.

When light is received by the light receivers 323, 333, and 342, thelight receivers 323, 333, and 342 output electrical pulse signals, andmeasurement data are generated based on the output electrical pulsesignals. The measurement data are transmitted from the analyzer body 1to the operation and display device 2, and undergo processing andanalysis in the operation and display device 2.

When the CBC measurement mode has been selected, the operation anddisplay device 2 counts the platelets by particle size analysis of theplatelets based on the measurement data of the first measuring unit D1.More specifically, the platelet count is analyzed by a histogram inwhich the platelet volume (units: fL) is plotted on the horizontal axis,and the number of platelets is plotted on the vertical axis.

The PLT measurement is performed by the first measuring unit D1 in thesample analyzer having the above configuration. When, for example,collapsed red blood cells contaminate the sample and the size of theparticles is measured by the first measuring unit D1, the value of thered blood cells which approach the size of platelets can not be ignoredand it becomes difficult to accurately count the platelets. In thesample analyzer of the first embodiment of the present invention, whenthe measurement data of a first PLT measurement is analyzed and it isdetermined that the measurement data are not reliable, the PLTmeasurement is then performed by the third measuring unit D3.

FIG. 11 is a flow chart showing the sequence of the processing by theCPU 21 of the operation and display device 2 of the first embodiment ofthe sample analyzer of the present invention. The CPU 21 of theoperation and display device 2 obtains measurement data as a PLTmeasurement result from the controller 11 of the analyzer body 1 (stepS1101).

The CPU 21 generates a histogram based on the obtained measurement data(step S1102), and displays the histogram on the display device 25. Thegenerated histogram plots the platelet volume on the horizontal axis andthe PLT count on the vertical axis.

The CPU 21 determines whether the measurement data are reliable (stepS1103). The process of determining whether the PLT measurement data arereliable is not particularly limited. In the present embodiment, themeasurement data are determined unreliable when the PLT count, that is,the number of platelets, is less than a predetermined value, or aplatelet distribution anomaly occurs.

FIG. 12 shows an illustration of the reliability determination based ona histogram. The histogram of FIG. 12 shots the PLT count (count values)plotted on the vertical axis and the platelet size plotted on thehorizontal axis. LD is the platelet size when a predetermined small sizeis as a frequency standard; UD is the platelet size when a predeterminedlarge number is set as the frequency standard. That is, when the PLTcount exceeds the LD frequency standard, the measurement data redetermined to be unreliable due to the high possibility of impuritiesaffecting the count. When the PLT count exceeds the UD frequencystandard, the measurement data are determined to be unreliable dueinadequate convergence when the count value is down, that is, the highpossibility of impurities.

The distribution width PDW is calculated for the 20% level when theheight of the peak of the PLT count is 100%, And a distribution anomalyis determined to exist when PDW is greater than a predetermined standardwidth.

FIG. 13 shows an illustration of a histogram based on PLT measurementdata. FIG. 13( a) shows a pattern example of a measurement datahistogram. As shown in FIG. 13( a), when the measurement data arereliable, the PLT count in LD and UD are adequately smaller than thefrequency standard, And the distribution width PDW is also smaller thanthe standard width.

FIG. 13( b) shows an example of a histogram when the UD platelet countvalue exceeds the frequency standard. In this case, the UD PLT frequencydoes not exceed the frequency standard, but the distribution width PDWdoes exceed the standard width, so a platelet distribution anomaly isdetermined.

FIG. 13( c) shows an example of a histogram when there are two or morepeaks in the PLT frequency. In this case, the LD and UD PLT frequency isadequately smaller than the frequency standard, but the distributionwidth PDW exceeds the predetermined standard width, so a plateletdistribution anomaly is determined. A distribution anomaly may also bedetermined when there are two or more distribution peaks even though thedistribution width PDW does not exceed the predetermined standard width.

FIG. 14 is a flow chart showing the sequence of the reliabilitydetermination process of the CPU 21 of the operation and display device2 of the first embodiment of the sample analyzer of the presentinvention. The CPU 21 of the operation and display device 2 generates ahistogram based on the obtained measurement data (step S1102), anddetermines whether a platelet distribution anomaly exists (step S1401).

When the CPU 21 has determined that a platelet distribution anomalyexists (step S1401: YES), the CPU 21 then determines the data areunreliable (step S1404), and the process continues to step S1104. Whenthe CPU 21 has determined that a platelet distribution anomaly does notexist (step S1401: NO), the CPU 21 then determines whether the plateletcount value is less than a predetermined value (step S1402).

When the CPU 21 has determined that the platelet count value is lessthan the predetermined value (step S1402: YES), the CPU 21 thendetermines the data are unreliable (step S1404), and the processcontinues to step S1104. It is believed that an increase in smallplatelets may lead to platelets leaked from the count target. When theCPU 21 has determined that the platelet count value exceeds apredetermined value (step S1402: NO), the CPU 21 determines the data arereliable (step S1403) and the process ends.

Returning now to FIG. 11, when the CPU 21 of the operation and displaydevice 2 has determined that the data are unreliable (step S1103: NO),the CPU 21 sends an instruction to again prepare a measurement samplefrom the same sample to the analyzer body 1 (step S1104). The controller11 of the analyzer body 1 receives the re-preparation instruction, andissues an instruction to the drive circuit to operate the samplepreparing section.

The CPU 21 sends an instruction to re-aspirate the re-preparedmeasurement sample to the analyzer body 1 (step S1105). The controller11 of the analyzer body 1 receives the re-aspiration instruction, andissues an instruction to the drive circuit 12 to operate the aspiratingtube 14.

The CPU 21 sends a measurement instruction to measure the re-aspiratedmeasurement sample by the third measuring unit D3, that is to performmeasurement using the optical type measuring device, to the analyzerbody 1 (step S1106). The controller 11 of the analyzer body 1 receivesthe measurement instruction and sends a measurement start signal to thethird measuring unit D3. When the CPU 21 determines that the data arereliable (step S1103: YES), the CPU 21 ends the process.

FIG. 15 shows an illustration of a scattergram representing the PLTre-measurement results of the first embodiment of the sample analyzer ofthe present invention. In the scattergram of FIG. 15, the forwardscattered light intensity is plotted on the vertical axis, and the sidefluorescent light intensity is plotted on the horizontal axis;measurements are performed by changing the stain (for example, NileBlue) to increase the degree of staining of the platelets. As is madeclear by FIG. 15, the platelet count value is concentrated in region1501, and there is no region in which the red blood cells and impuritiesintersect. Therefore, the blood can be analyzed with excellent precisionby changing the detection method of the first embodiment, that is, thesecond detection condition according to the reliability of the firstmeasurement data.

Since the measurement sample is re-prepared based on the same sample,and the operations of the sample preparing section and the aspiratingtube 14 controlled so as to re-aspirate the prepared measurement sampleonly when reliable measurement data can not be obtained as the detectionresults of the predetermined components, the reagent used in preparingthe sample is conserved, and the increase in the number of measurementprocesses can be limited to a minimum.

Second Embodiment

The structure of the sample analyzer of the second embodiment of thepresent invention is identical to that of the first embodiment with likeparts designated by like reference numbers, and further detaileddescription is therefore omitted. The second embodiment, like the firstembodiment, provides the selection of the CBC+RET measurement mode(second measurement mode), but does not provide the CBC measurement mode(first measurement mode).

The operation of the sample analyzer is described below when the CBC+RETmeasurement mode (second measurement mode) has been selected in thesecond embodiment. In the analyzer body 1 of the second embodiment, whenthe CBC+RET measurement mode is selected, the RBC count and PLT countare performed by the first measuring unit D1, and the WBC measurement,RET measurement, and PLT measurement are performed by the thirdmeasuring unit (detector) D3.

Since main structure of the first measuring unit D1, which is anelectrical resistance type measuring device, and the structure of thethird measuring unit D3, which is an optical type measuring device, areidentical to those of the first embodiment, like parts are designated bylike reference numbers, and further detailed description is omitted.

When the CBC+RET measurement mode (second measurement mode) has beenselected, the operation and display device 2 the platelets arerespectively counted by analyzing the particle size of the plateletsbased on the measurement data of the first measuring unit D1 and themeasurement data of the third measuring unit D3. More specifically, inthe case of the measurement data of the first measuring unit D1, theplatelet count is analyzed by creating a histogram and plotting theplatelet volume on the horizontal axis and plotting the PLT frequency onthe vertical axis. In the case of the measurement data of the thirdmeasuring unit D3, the platelet count is analyzed by creating ahistogram and plotting the forward scattered light intensity on thehorizontal axis and plotting the PLT frequency (platelet count) on thevertical axis.

In the sample analyzer of the above configuration, the PLT measurementis performed by both the first measuring unit D1 and the third measuringunit D3. Although the size of a predetermined component of the sample isrespectively measured by the first measuring unit D1 using an electricalresistance type measuring device and by the third measuring unit D3using an optical type measuring device, the numerical value of thenumber of red blood cells approaching the size of platelets can not beignored when, for example, collapsed red blood cells are included in thesample, thereby making it difficult to accurately count the number ofplatelets. In the sample analyzer of the second embodiment of thepresent invention, the reliability of the first PLT measurementsperformed by the first measuring unit D1 and third measuring unit D3 arerespectively analyzed, and the measurement data with the higherreliability are used. When both measurement data are reliable, themeasurement data of the third measuring unit D3 are used, and when bothmeasurement data are unreliable, a second PLT measurement is performedby the third measuring unit D3.

FIG. 16 is a flow chart showing the sequence of the processing by theCPU 21 of the operation and display device 2 of the second embodiment ofthe sample analyzer of the present invention. The CPU 21 of theoperation and display device 2 obtains the respective measurement dataof the first measuring unit D1 and the third measuring unit D3 from thecontroller 11 of the analyzer body 1 (step S1601). Note that in themeasurement performed by the third measuring unit D3, the CPU 21transmits a predetermined amplification factor to the amplifiers 324,334, 342. Thus, the light receiving systems 320, 330, 340, havepredetermined detection sensitivities.

The CPU 21 generates a histogram based on the obtained measurement dataof the first measuring unit D1 (step S1602), and displays the histogramon the display device 25. The generated histogram plots the plateletparticle size on the horizontal axis and the PLT count on the verticalaxis.

The CPU 21 generates a histogram based on the obtained measurement dataof the third measuring unit D3 (step S1603), and displays the histogramon the display device 25. The generated histogram plots the sidefluorescent light intensity on the horizontal axis, and plots theforward scattered light intensity on the vertical axis.

The CPU 21 determines whether the measurement data of the thirdmeasuring unit D3 are reliable (step S1604). The process of determiningwhether the PLT measurement data are reliable is not particularlylimited. In the second embodiment, similar to the first embodiment, themeasurement data are determined unreliable when the PLT count, that is,the number of platelets, is less than a predetermined value, or aplatelet distribution anomaly occurs.

FIG. 17 is a flow chart showing the sequence of the reliabilitydetermination process of the CPU 21 of the operation and display device2 of the second embodiment of the sample analyzer of the presentinvention. The CPU 21 of the operation and display device 2 generates ahistogram based on the obtained measurement data of the first measuringunit D1 (step S1602), and generates a scattergram based on the obtainedmeasurement data of the third measuring unit D3 (step S1603), thendetermines whether a platelet distribution anomaly exists based on themeasurement data of the third measuring unit D3 (step S1701).

FIG. 18 shows an example of a scattergram of the first PLT measurementresult by the third measuring unit D3 of the second embodiment of thesample analyzer of the present invention. In the scattergram of FIG. 18,the forward scattered light intensity is plotted on the vertical axisand the side fluorescent light intensity is plotted on the horizontalaxis. In the example of FIG. 18, there is a region of overlap betweenthe PLT display region 181 and the impurity display region 182, makingit difficult to accurately differentiate the regions.

FIG. 19 shows another example of a scattergram of the first PLTmeasurement result by the third measuring unit D3 of the secondembodiment of the sample analyzer of the present invention. In thescattergram of FIG. 19, the forward scattered light intensity is plottedon the vertical axis and the side fluorescent light intensity is plottedon the horizontal axis. In the example of FIG. 19, there is a region ofoverlap between the PLT display region 191 and the impurity displayregion 192, making it difficult to accurately differentiate the regions.The number of occurrences of particles is counted in the predeterminedregion in which it is difficult to differentiate particles on thescattergrams shown in FIGS. 18 and 19, so that whether a plateletdistribution anomaly occurs can be determined according to whether thecounted occurrences is greater than a predetermined number.

Returning now to FIG. 17, when the CPU 21 of the operation and displaydevice 2 has determined that a platelet distribution anomaly exists(step S1701: YES), the CPU 21 then determines that the measurement dataof the third measuring unit D3 are unreliable (step S1704), and theprocess continues to step S1705. When the CPU 21 determines that aplatelet distribution anomaly does not exist (step S1701: NO), the CPU21 then determines whether the platelet count is less than apredetermined value based on the measurement data of the third measuringunit D3 (step S1702).

When the CPU 21 has determined that the platelet count value is lessthan the predetermined value (step S1702: YES), the CPU 21 thendetermines that the measurement data of the third measuring unit D3 areunreliable (step S1704), and the process continues to step S1705). It isbelieved that an increase in small platelets may lead to plateletsleaked from the count target. When the CPU 21 determines that theplatelet count value exceeds the predetermined value (step S1702: NO),the CPU 21 then determines that the measurement data of the thirdmeasuring unit D3 are reliable (step S1703), and the process continuesto step S1606.

The CPU 21 determines whether a platelet distribution anomaly existsbased on the measurement data of the first measuring unit D1 (stepS1705).

When the CPU 21 has determined that a platelet distribution anomalyexists (step S1705: YES), the CPU 21 then determines that themeasurement data of the first measuring unit D1 are unreliable (stepS1708), and the process continues to step S1608). When the CPU 21determines that a platelet distribution anomaly does not exist (stepS1705: NO), the CPU 21 then determines whether the platelet count isless than a predetermined value based on the measurement data of thefirst measuring unit D1 (step S1706).

When the CPU 21 has determined that the platelet count value is lessthan the predetermined value (step S1706: YES), the CPU 21 thendetermines that the measurement data of the first measuring unit D1 areunreliable (step S1708), and the process continues to step S1608). It isbelieved that an increase in small platelets may lead to plateletsleaked from the count target. When the CPU 21 determines that theplatelet count value exceeds the predetermined value (step S1706: NO),the CPU 21 then determines that the measurement data of the firstmeasuring unit D1 are reliable (step S1707), and the process continuesto step S1607.

Returning now to FIG. 16, when the CPU 21 of the operation and displaydevice 2 has determined that the measurement data of the third measuringunit D3 are unreliable (step S1604: NO), the CPU 21 then determineswhether the measurement data of the first measuring unit D1 are reliable(step S1605). The method for determining whether the data are reliableis identical to the method of the first embodiment.

When the CPU 21 has determined that the measurement data of the firstmeasuring unit D1 are unreliable (step S1605: NO), the CPU 21 thentransmits an instruction to re-prepare a measurement sample from thesame sample to the analyzer body 1 (step S1608). The controller 11 ofthe analyzer body 1 receives the re-preparation instruction, and issuesan instruction to the drive circuit to operate the sample preparingsection.

The CPU 21 sends an instruction to re-aspirate the re-preparedmeasurement sample to the analyzer body 1 (step S1609). The controller11 of the analyzer body 1 receives the re-aspiration instruction, andissues an instruction to the drive circuit 12 to operate the aspiratingtube 14.

The CPU 21 transmits, to the analyzer body 1, a setting changeinstruction for changing the optical sensitivity so as to be higher thanfor the first measurement when measuring the re-aspirated measurementsample by the third measuring unit D3, that is, the optical typemeasuring device (step S1610). The controller 11 of the analyzer body 1receives the setting change instruction and transmits a setting changesignal for changing the optical sensitivity (detection sensitivity) tothe third measuring unit D3. Specifically, the CPU 21 transmits anamplification factor which is higher than the amplification factor sentin step S1601 to the amplifiers 324, 334, 344. Thus, the light receivingsystems 320, 330, and 340 have higher detection sensitivities than thedetection sensitivities in step S1601.

The CPU 21 sends a measurement instruction to measure the re-aspiratedmeasurement sample by the third measuring unit D3, that is, to performmeasurement using the optical type measuring device, to the analyzerbody 1 (step S1611). The controller 11 of the analyzer body 1 receivesthe measurement instruction and sends a measurement start signal to thethird measuring unit D3.

When the CPU 21 has determined that the measurement data of the thirdmeasuring unit D3 are reliable (step S1604: YES), the CPU 21 then usesthe measurement data of the third measuring unit D3 as the PLTmeasurement data (step S1606), and the process ends. When the CPU 21 hasdetermined that the measurement data of the first measuring unit D1 arereliable (step S1605: YES), the CPU 21 then uses the measurement data ofthe first measuring unit D1 as the PLT measurement data (step S1607),and the process ends.

FIG. 20 shows an example of a scattergram of the second PLT measurementresult by the third measuring unit D3 of the second embodiment of thesample analyzer of the present invention. In the scattergram of FIG. 20,the forward scattered light intensity is plotted on the vertical axisand the side fluorescent light intensity is plotted on the horizontalaxis. In the example of FIG. 20, relatively small size platelets can beaccurately measured by increasing the photosensitivity, and when stainis changed (for example, to Nile Blue) to increase the degree ofstaining of the platelets, the PLT display region 201 can be betterdifferentiated and displayed. Therefore, blood can be analyzed withgreater precision by performing a second measurement by the thirdmeasuring unit D3 only when the first detection result is unreliable.

Since the measurement sample is re-prepared based on the same sample,and the operations of the sample preparing section and the aspiratingtube 14 are controlled so as to re-aspirate the prepared measurementsample only when reliable measurement data can not be obtained as thedetection results of the predetermined components, the reagent used inpreparing the sample is conserved, and the increase in the number ofmeasurement processes can be limited to a minimum.

Note that although the first and second embodiments have been describedin terms of changing the photosensitivity of the third measuring unit D3and re-measuring using the third measuring unit D3 as a detectioncondition, the present invention is not limited to changing thedetection condition. For example, the intensity of the irradiating lightmay also be changed.

Although the first and second embodiments have been described by way ofexamples of blood analyzers for analyzing blood cells contained in bloodusing the blood as a sample, the present invention is not limited tothis arrangement inasmuch as similar effectiveness can be expected whenthe present invention is applied to a sample analyzer for analyzing asample containing bioparticles in urine. Although the analysis resultsare displayed on the operation and display device 2 in the first andsecond embodiments, the present invention is not particularly limited tothis arrangement inasmuch as the analysis results may also be displayedon the display device of another computer connected over a network.

Although the first and second embodiments employ an electricalresistance type detector as the first measuring unit D1 and employ anoptical type detector as the third measuring unit D3, the presentinvention is not limited to this arrangement inasmuch as an optical typedetector may be used as the first measuring unit D1 and an electricalresistance type detector may be used as the third measuring unit D3, orat least one of the first measuring unit D1 and third measuring unit D3may be a combination detector which combines optical type and electricalresistance type detection.

Although the photosensitivity (first detection condition) used in thethird measuring unit D3 in step S1601 is a photosensitivity fordetecting platelets and red blood cells, and the photosensitivity(second detection condition) used in the third measuring unit D3 in stepS1611 is a photosensitivity for detecting only platelets in the secondembodiment, the present invention is not limited to this arrangementinasmuch as the first detection condition may be changed to aphotosensitivity for detecting reticulocytes, platelets, and red bloodcells, and the second detection condition may be changed to aphotosensitivity for detecting platelets and red blood cells. Note thatin order to obtain a highly reliable measurement result, the type ofcomponent to be detected would preferably utilize the first detectioncondition more often than the second detection condition.

Although the first and second embodiments are described in terms of ablood analyzer in which blood within a single collection tube 3 isplaced at a predetermined position within the analyzer body 1, it is tobe understood that similar effectiveness is attained in the case of asample analyzer that performs desired measurements of blood by moving arack holding a plurality of collection tubes 3 via a conveyor mechanism.In this case, when blood must be remeasured due to unreliablemeasurement data, an instruction for moving the corresponding collectiontube 3 must be sent to the controller of the conveyor mechanism so as toretransport the corresponding collection tube 3 to the position of theaspirating tube 14. Of course, when the aspirating tube 14 is a movabletype, an instruction may also be issued to move the position of theaspirating tube 14 to the position of the corresponding collection tube3.

1. A sample analyzer comprising: a sample preparing section forpreparing first and second measurement sample including reagent andsample; a first detector for detecting a predetermined component in thefirst measurement sample prepared by the sample preparing section; asecond detector for detecting the predetermined component in the secondmeasurement sample prepared by the sample preparing section; and acontroller configured for performing operations, comprising: (a)controlling the first detector to detect the predetermined component inthe first measurement sample prepared by the sample preparing section;(b) determining the reliability of the result detected by the firstdetector; (c) controlling the sample preparing section to prepare thesecond measurement sample from the same sample when the result has beendetermined to be unreliable; and (d) controlling the second detector todetect the predetermined component in the second measurement sample. 2.The sample analyzer according to claim 1, wherein the first detector andthe second detector are configured to detect the predetermined componentby mutually different detection principles.
 3. The sample analyzeraccording to claim 2, wherein the first detector comprises: a first flowcell through which the first measurement sample flows; and an electricalinformation obtainer for obtaining electrical information when the firstmeasurement sample flows through the first flow cell; and the seconddetector comprises: a second flow cell through which the secondmeasurement sample flows; a light emitting unit for irradiating light onthe second measurement sample flowing through the second flow cell; anda light receiving unit for receiving light from the second measurementsample irradiated by the light from the light emitting unit.
 4. Thesample analyzer according to claim 3, wherein the sample is blood; andthe predetermined component is platelet in the blood.
 5. The sampleanalyzer according to claim 4, wherein the second detector is configuredto further detect white blood cells in the blood.
 6. The sample analyzeraccording to claim 1, wherein in step (c), the controller controls thesample preparing section to prepare the second measurement sample fromthe same sample and a different reagent than the reagent used in thefirst measurement sample.
 7. The sample analyzer according to claim 1,wherein the sample is blood; and the predetermined component is plateletin the blood.
 8. The sample analyzer according to claim 7, wherein instep (b), the controller determines the result is unreliable when theplatelet count value is less than a predetermined value or when aplatelet distribution anomaly occurs.
 9. A sample analyzer comprising: asample preparing section for preparing first and second measurementsample including reagent and sample; a first detector for detecting apredetermined component in the first and second measurement sampleprepared by the sample preparing section; and a controller configuredfor performing operations, comprising: (a) controlling the firstdetector to detect the predetermined component in the first measurementsample prepared by the sample preparing section using a first detectioncondition; (b) determining the reliability of the result detected by thefirst detector; (c) controlling the sample preparing section to preparethe second measurement sample from the same sample when the result hasbeen determined to be unreliable; and (d) controlling the first detectorto detect the predetermined component in the second measurement sampleusing a second detection condition which is different from the firstdetection condition.
 10. The sample analyzer according to claim 9,wherein the first detection condition is a condition for detecting aplurality of types of components, and the second detection condition isa condition for detecting fewer types of components than the firstdetection condition.
 11. The sample analyzer according to claim 10,wherein the first detection condition is a condition for detecting atleast two types of components, and the second detection condition is acondition for detecting only one type of component.
 12. The sampleanalyzer according to claim 9, further comprising: a second detector fordetecting the predetermined component in third measurement sampleincluding sample and reagent prepared by the sample preparing section;wherein the controller is configured for performing further operations,comprising determining the reliability of the result of the seconddetector, wherein the controller determines the result is unreliablewhen the result detected by the first detector and the result detectedby the second detector are both unreliable.
 13. The sample analyzeraccording to claim 12, wherein the controller accepts a resultdetermined to be reliable when one or the other of the result detectedby the first detector and the result detected by the second detector hasbeen determined to be reliable.
 14. The sample analyzer according toclaim 12, wherein the second detector comprises: a first flow cellthrough which the third measurement sample flows; and an electricalinformation obtainer for obtaining electrical information when the thirdmeasurement sample flows through the first flow cell; and the firstdetector comprises: a second flow cell through which the first andsecond measurement sample flows; a light emitting unit for irradiatinglight on the first and second measurement sample flowing through thesecond flow cell; and a light receiving unit for receiving light fromthe first and second measurement sample irradiated by the light from thelight emitting unit; and the controller uses the result detected by thefirst detector when the result detected by the first detector has beendetermined to be reliable, regardless of the reliability of the resultdetected by the second detector.
 15. The sample analyzer according toclaim 9, wherein the first detector comprises: a second flow cellthrough which the measurement sample flows; a light emitting unit forirradiating light on the first and second measurement sample flowingthrough the second flow cell; and a light receiving unit for receivinglight from the first and second measurement sample irradiated by thelight from the light emitting unit; the first and second detectionconditions relate to the light detection sensitivity of the lightreceiving unit, and the detection sensitivity in the second detectioncondition is higher than the detection sensitivity in the firstdetection condition.
 16. The sample analyzer according to claim 15,wherein the light receiving unit comprises a detecting part fordetecting light and for outputting signal corresponding to the amount ofdetected light, and an amplifier for amplifying the signal output fromthe detecting part; and the first and second detection conditions relateto the degree of amplification by the amplifier.
 17. The sample analyzeraccording to claim 9, wherein in step (c), the controller controls thesample preparing section to prepare the second measurement sample fromthe same sample and a different reagent than the reagent used in thefirst measurement sample.
 18. The sample analyzer according to claim 9,wherein the sample is blood; and the predetermined component is plateletin the blood.
 19. The sample analyzer according to claim 18, wherein instep (b), the controller determines the result is unreliable when aplatelet distribution anomaly occurs.
 20. The sample analyzer accordingto claim 19, wherein the controller determines there is a plateletdistribution anomaly when the platelet distribution region at leastpartially overlaps the distribution region of another component in ascattergram representing the distributions of components in blood.